Adipogenesis is the formation of fat or fatty tissue. A fat cell develops as internally produced lipid droplets coalesce into a single large mass. More recently, studies of adipogenesis have proceeded with the hope that manipulation of this process in humans might lead to a reduction in the burden of obesity and diabetes.
Obesity, defined as an increase in adipose tissue mass, is the most prevalent nutritional disorder in industrialized countries and is a growing problem in developing countries. An increase in adipose tissue mass can be the result of the production of new fat cells through the process of adipogenesis and/or the deposition of increased amounts of cytoplasmic triglyceride per cell. Eventually, cellulite results due to enhanced adipogenesis and accumulation of chunks of adipocytes under the skin dermis.
Obesity is described as a global epidemic and overweight and obese individuals (BMI of 25 and above) are at increased risk for various chronic physical ailments and psychological problems such as depression, eating disorders and low self esteem.
The prevalence of overweight and obesity is increasing throughout the world's population. The World Health Organization (WHO) reports that more than one billion adults are overweight and at least 300 million of them are clinically obese. WHO considers obesity to be one of the top 10 causes of preventable death worldwide.
There is a constant need and search for safe natural approach to help manage obesity and its related socio-economic consequences.
Garcinol, a polyisoprenylated benzophenone derivative isolated from Garcinia species is a well-known anti-oxidant (i.e., emulsified garcinol suppressed superoxide anion comparably to DL alpha-tocopherol), anti-carcinogen and also has anti-microbial properties.
Garcinol, isolated from Garcinia sp. fruit rind exhibits anti-oxidant and chemoprotective properties (1). In one experiment, rats fed a garcinol diet (0.01% and 0.05%) showed a significantly reduced development of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) as compared to control animals. Feeding of garcinol significantly elevated liver glutathione S-transferase, quinone reductase activities, suppressed O2 and NO generation and expression of iNOS and COX-2 proteins. These findings suggest a possible chemopreventive mechanism of garcinol.
Garcinol and isogarcinol were evaluated for their antibacterial activity against methicillin-resistant Staphylococcus aureus (2). These compounds showed a minimum inhibitory concentration at 3.1-12.5 micrograms/ml, or nearly equal to that of the antibiotic, vancomycine.
Garcinol's role as a potent inhibitor of histone acetyltransferases (HATs) both in vitro and in vivo was reported by Tapas et al in 2004 (“Polyisoprenylated Benzophenone, Garcinol, a Natural Histone Acetyltransferase Inhibitor, Represses Chromatin Transcription and Alters Global Gene Expression”, The Journal of Biological Chemistry, Vol. 279, No. 32, Issue of August 6, pp. 33716-33726, 2004)
Anthocyanins are one class of flavanoid compounds, which are widely distributed plant polyphenols. They occur in all tissues of higher plants, including leaves, stems, roots, flowers, and fruits. There is considerable evidence that dietary anthocyanin pigments have preventative and therapeutic roles in a number of human diseases. The chemical basis for these desirable properties of anthocyanins is believed to be related to their antioxidant capacity, ability to scavenge and trap free radicals that damage biomolecules.
In 1982, N. Krishnamurthy et al. (3) isolated anthocyanin pigments from the fresh red ripe fruits of Kokam (Garcinia indica). The rind portion was separated from the rest of the fruit and was macerated in a blender using methanol containing 1% HCl for three times. The extracts were combined, filtered and concentrated in vacuo at 30° C. Paper chromatography of the Kokam pigment extract showed two anthocyanin bands. The slower moving band was designated as B1 and the other B2. The total anthocyanin concentration was estimated to be 2.4 percent on a dry weight basis; the ratio of B1 to B2 is 1:4.
Majeed et al (U.S. Pat. No. 7,063,861) discloses a composition comprising hydroxycitric acid in combination with either one or both of garcinol and anthocyanin and its use in weight loss therapy in animal subjects.
It is reported that dietary resveratrol (3,4′,5-trihydroxy-trans-stilbene) at 50 parts per million suppressed blood serum lipid peroxidase levels in rats and dose-dependently suppressed serum triglyceride levels, VLDL and LDL cholesterol levels [Miura, D.; Miura, Y.; Yagasaki, K. Hypolipidemic action of dietary resveratrol, a phytoalexin in grapes and red wine, in hepatoma-bearing rats. Life Sci. 2003, 73, 1393-400]. Naokatu Arakaki et al reported that treatment of differentiated 3T3-L1 adipocytes with H+-ATP synthase inhibitors (resveratrol; piceatannol) lead to a decrease in cytosolic lipid droplet accumulation.
Rimando et al document that pterostilbene (3,5-dimethoxy-4′-hydroxystilbene), a natural analog of resveratrol acts as a PPARα agonist and may be a more effective hypo-lipidemic agent than resveratrol itself [J. Agric. Food Chem. 2005, 53, 3403-3407]. This documentation is further validated by Marudhamuthu Amarnath Sateesh and Leelavinothan Pari, who observed that pterostilbene significantly, lowered levels of triglycerides, phospholipids, free fatty acids and total cholesterol in the serum, liver and kidneys of diabetic rats [Journal of Applied Biomedicine, Volume 5 (2008), No 1).
The present invention provides a composition for inhibiting adipogenesis and thereby its use in treating obesity or weight loss.